HBcAg (residues1-183) has been expressed in E.coli where it assembles in the bacterial cytoplasm into icosahedral capsids. Deletion of the polybasic C-terminal 34 residues (protamine domain) produces assembly-competent protein (residues 1- 149) suitable for structural analysis. The structure of the capsids has been previously determined by cryo-electron microscopy and by X-ray crystallography. The closely related HBeAg is a soluble secreted protein thought to modulate both the innate and adaptive immune responses to favor persistent or chronic infection. HBeAg is also an important clinical marker of HBV infection. We used an HBeAg-specific antibody fragment (Fab) as a chaperone to assist crystallization and structure determination of HBeAg. The HBeAg structure precludes capsid assembly and forms a distinct antigenic repertoire, explaining why HBcAg and HBeAg are cross-reactive at the T cell level (through sequence identity) but not at the B cell level. HBeAg is thought to regulate immune responses by direct interaction with proteins, for example Mal, that regulate the innate immune system. Using the structure of HBeAg, we have been modeling its interaction (docking) with target proteins as a guide for new structural studies. The direct targeting of HBeAg has potential for the treatment of chronic HBV. Towards this goal we have used phage display technology to generate a panel of humanized Fabs against HBeAg. Some of these Fabs were shown to have unprecedented high binding affinities against HBeAg. The structure of selected Fab-HBeAg complexes is being attempted to map the antibody-protein binding interaction as a prelude to potential drug design. In addition, we have used the anti-HBeAg Fabs to develop a new and highly specific HBeAg for research and clinical purposes.